Role of Antimicrobial Peptide Bac7 in Regulating the adeIJK Efflux Pump in Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates

Document Type : New and original researches in the field of Microbiology.

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Institute of Genetic Engineering and Biotechnology for postgraduate studies, University of Baghdad, Baghdad, Iraq

Abstract

Background: Acinetobacter baumannii is one of the leading and serious pathogens causing multidrug-resistant (MDR) hospital-acquired infections and efflux pumps, such as adeIJK, contribute significantly to well-studied intrinsic antibiotic resistance. Bioactive molecules such as antimicrobial peptides (AMPs), including Bac7, have gained considerable traction because their mechanisms of action are quite distinct. Objective: To evaluate the effect of the antimicrobial peptide Bac7 on the expression and activity of the adeIJK efflux pump in carbapenem-resistant Acinetobacter baumannii. Methodology: One hundred fifty clinical specimens were collected from two hospitals in Baghdad. Isolation and identification of A. baumannii were done using VITEK 2 system, and also molecular identification was used by specific gene blaOXA-51 with polymerase chain reaction.  Antimicrobial activity of Bac7 was assessed by minimum inhibitory concentration (MIC) determination against carbapenem-resistant isolates using microdilution method with resazurin dye. Bac7 treatment effects on the expression of the efflux pump genes adeJ and adeK were determined using quantitative Real-time polymerase chain reaction (RT-PCR). Results: the highest incidence of A. baumannii isolation (43.3 %) was associated with clinical specimens; the overall incidence of A. baumannii isolation from burn wound samples. Multidrug resistance was recorded in 64.6% of isolates at high levels. Bac7 exhibited obvious MIC values among seven multi-drug resistant isolates of effective antibacterial activity with MICs range from 62.5 to 125 μg/ml. Gene expression analyses showed that exposure of Bac7 led to downregulation of adeJ (0.23 fold) while there was a slight upregulation of fold change (1.8 fold) of adeK (1.17-fold), implying that Bac7 might not be a potent substrate of the AdeIJK efflux pump. Conclusion: The antimicrobial peptide Bac7 displays antibacterial activity against carbapenem-resistant A. baumannii and seems to evade the adeIJK efflux system or only have minimal cross-interaction. Particularly in cases of dominant efflux-mediated resistance, these findings confirm the promise of Bac7 as a novel therapeutic agent to treat MDR A. baumannii infections.

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